INDUCTION OF APOPTOSIS IN MATURE T-CELLS BY TUMOR-NECROSIS-FACTOR

T-CELL receptor-induced apoptosis regulates immune responses and can result from interactions between Fas (Apo1/CD95) and Fas ligand (FasL)(1-12). Mutations in the genes for Fas and FasL cause disorders resembling human autoimmune diseases in lpr and gld mice, respectively(13,14). However, peripheral T-cell deletion takes place in lpr mice, acid autoimmune syndromes occur in mouse strains without Fas or FasL defects(15,16). Here we show that tumour necrosis factor (TNF) can mediate mature T-cell receptor-induced apoptosis through the p75 TNF receptor. Blockage of both TNF and Fast is required to abrogate T-cell death and TNF mediates the death of most CD8(+) T cells, whereas FasL mediates the death of most CD4(+) T cells. Our results suggest that autoregulatory apoptosis of the mature T cells can occur by two distinct molecular mechanisms.